Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies

Overview

Journal BioDrugs

Specialties Allergy & Immunology
Genetics
Pharmacology

Date 2018 Aug 23

PMID 30132211

Citations 58

Authors

Bushra Husain

Diego Ellerman

Affiliations

Soon will be listed here.

Abstract

Bispecific antibodies have moved from being an academic curiosity with therapeutic promise to reality, with two molecules being currently commercialized (Hemlibra and Blincyto) and many more in clinical trials. The success of bispecific antibodies is mainly due to the continuously growing number of mechanisms of actions (MOA) they enable that are not accessible to monoclonal antibodies. One of the earliest MOA of bispecific antibodies and currently the one with the largest number of clinical trials is the redirecting of the cytotoxic activity of T-cells for oncology applications, now extending its use in infective diseases. The use of bispecific antibodies for crossing the blood-brain barrier is another important application because of its potential to advance the therapeutic options for neurological diseases. Another noteworthy application due to its growing trend is enabling a more tissue-specific delivery or activity of antibodies. The different molecular solutions to the initial hurdles that limited the development of bispecific antibodies have led to the current diverse set of bispecific or multispecific antibody formats that can be grouped into three main categories: IgG-like formats, antibody fragment-based formats, or appended IgG formats. The expanded applications of bispecific antibodies come at the price of additional challenges for clinical development. The rising complexity in their structure may increase the risk of immunogenicity and the multiple antigen specificity complicates the selection of relevant species for safety assessment.

Citing Articles

Facilitating high throughput bispecific antibody production and potential applications within biopharmaceutical discovery workflows.

Fawcett C, Tickle J, Coles C MAbs. 2024; 16(1):2311992.

PMID: 39674918 PMC: 10883111. DOI: 10.1080/19420862.2024.2311992.

The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.

Ellerman D BioDrugs. 2024; 39(1):75-102.

PMID: 39673023 DOI: 10.1007/s40259-024-00691-0.

Sequence and Configuration of a Novel Bispecific Antibody Format Impacts Its Production Using Chinese Hamster Ovary (CHO) Cells.

Hussain H, Ozanne A, Patel T, Vito D, Ellis M, Hinchliffe M Biotechnol Bioeng. 2024; 122(2):435-444.

PMID: 39587782 PMC: 11718431. DOI: 10.1002/bit.28879.

End-To-End Automated Intact Protein Mass Spectrometry for High-Throughput Screening and Characterization of Bispecific and Multispecific Antibodies.

Niu B, Lee B, Chen W, Alberto C, Betancourt Moreira K, Compton P Anal Chem. 2024; 96(45):18287-18300.

PMID: 39479787 PMC: 11562946. DOI: 10.1021/acs.analchem.4c04833.

Advancements in Ocular Therapy: A Review of Emerging Drug Delivery Approaches and Pharmaceutical Technologies.

Giri B, Jakka D, Sandoval M, Kulkarni V, Bao Q Pharmaceutics. 2024; 16(10).

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